Response to carbidopa/levodopa (CD/LD), the most efficacious therapy in Parkinson's disease (PD), is often variable among patients. At initiation of therapy, some patients require higher doses than others in order to achieve the same benefit. Still others never fully respond to CD/LD despite being on recommended doses. As the disorder progresses incomplete responses to CD/LD characterized by both a reduced quality of response as well as a shorter duration of response become typical. There is strong evidence to suggest that LD availability may, in part, be responsible for these sub optimal responses. CD has a critical impact on LD availability since it reduces the peripheral breakdown of LD by inhibiting peripheral LD decarboxylation and allows more LD to enter brain, the site of clinical action. Consequently, trying to individualize CD therapy could prove to be a most important therapeutic strategy for PD. The opportunity to determine the best CD dose for any individual patient was previously limited by the unavailability of safe, practical techniques to measure inhibition of peripheral LD decarboxylation. Physical Sciences Inc. (PSI) in collaboration with its STTR partner, Boston VA Healthcare System, and Cambridge Isotope Laboratories(CIL) proposes using stable isotope labeled LD and a 13CO2 breath test to determine if individualizing CD doses will improve treatment of PD. Stable isotope labeled LD is not radioactive and therefore presents no radiation risk to patients, investigators or environment. We hypothesize that individualizing CD therapy for each patient will provide for significant improvement over current therapy that uses standardized CD/LD tablets. Our preliminary data suggests that the current CD doses in commercially available CD/LD tablets may be inadequate for many PD patients. The ultimate goal of the proposed STTR project is to develop a simple, office-based breath test that can be used to individualize and optimize carbidopa therapy in Parkinson disease. PUBLIC HEALTH RELEVANCE: The proposed research seeks to develop a simple, safe and non-invasive breath-based assay that can be used by physicians to individualize the optimal dosing of carbidopa in carbidopa/levodopa therapy for Parkinson's disease (PD). If successful, this new pharmacologic probe could help reduce the variable response to carbidopa/levodopa (SinemetTM) that is often observed among PD patients and enhance the benefit of this very important PD therapy. The ability to diminish "off" time in PD would be a significant advance in the therapeutics of PD. As many as 1 million Americans suffer from PD. It is estimated that 70 to 80% of treated PD patients are on levodopa therapy.